Zebrafish: modeling senescence in the context of disease and regeneration

Abstract

Cellular senescence is a natural biological process characterized by permanent and irreversible
state of cellular arrest, mitochondrial alteration, and secretion of senescence-associated phenotype
(SASP) components. Several factors can induce senescence, including DNA damage,
oxidative stress, and neuroinflammation, these factors have also been linked to several disorders
such as Alzheimer’s, Parkinson’s, cancer, among others. The increased presence of senescent cells
among different diseases suggests the importance of senescence in the pathophysiology of a great
number of disorders, thus the need for different models that could help deepen our understanding of
the molecular mechanisms of senescence, identify possible targets for therapeutic interventions, and
arising challenges. In addition to in vitro models, most senescent research has come from classical
model species, i.e., mouse and rat. Senescence is highly
conserved; different studies have shown that senescent cells seem to accumulate in all vertebrate
organisms and that several associated genes show similar expression patterns, opening the door to
new vertebrate models. The zebrafish has become a strong emerging model for different diseases,
such as cancer, inflammation, neurodegeneration, among others; it shares multiple advantages with
classical models, such as well-established genome editing tools and a fully sequenced genome.
Additionally, zebrafish exhibit multiple advantages, including high fecundity for robust statistical
analysis, external fertilization, and optical transparency that enables powerful imaging capabilities
and makes it a versatile model for experimental manipulation and structural visualization. Here we
present the zebrafish as a model that can contribute significantly to our understanding of the processes
involved in senescence and age-related diseases.